• Avastin may impair the wound healing process and can induce postoperative wound healing complications in patients.
• To avoid surgical wound healing complications, perioperative precautions are critical.
• Roche recommendations include
• withhold Avastin for elective surgery
• do not initiate Avastin for at least 28 days after surgery or until the surgical wound is fully healed, and
• discontinue Avastin in patients who develop necrotising fasciitis.

• Published guidelines suggest stopping Avastin for 6-8 weeks before major surgery, and reinitiate 4-8 weeks after major surgery. Furthermore, data exists regarding the use of Avastin in patients undergoing minor surgery.

Avastin may adversely impact the wound healing process due to its inhibition of angiogenesis. Wound healing complications are a known adverse drug reaction of Avastin and fatal events have been reported in clinical trials and in the post-marketing setting.[1]

Data from metastatic colorectal trials, showed that if patients were taking Avastin at the time of surgery, an increase in the incidence of wound healing complications arose within 60 days of surgery. The incidence of complications varied between 10% (4/40) and 20% (3/15).[1]

Therefore, to avoid surgical wound healing complications, perioperative precautions are critical. Refer to your local Avastin label for information on the use of Avastin before and after surgery. 

Various recommendations are available on the use of Avastin prior to major elective surgery. The interested reader is directed to the relevant references for further information.

Roche recommendation

Avastin should be withheld prior to major elective surgery. For your reference, the half life of Avastin is between 18-20 days [1].

Guidelines from pivotal Avastin clinical trials

In the pivotal Avastin clinical trials Avastin was withheld for between 4-6 weeks prior to a surgical procedure.[2-14]

Major surgical procedures were classed as invasive procedures requiring general anaesthesia, and included open biopsies.

Published guidelines and clinical opinion

Published guidelines and clinical opinions are available which recommend to allow for at least 6 to 8 weeks between the last dose of Avastin and elective surgery;[15-19] this corresponds to two half-lives of Avastin.

Roche recommendations

Do not initiate Avastin for at least 28 days after major surgery or until the surgical wound is fully healed.[1]

Necrotising fasciitis including fatal cases, has rarely been reported in patients treated with Avastin.[1] Discontinue Avastin in patients who develop necrotising fasciitis.

Exclusion criteria in pivotal Avastin clinical trials

Patients were excluded from the Avastin pivotal trials if they had major surgery within 28 days of study initiation.[2-14]

Published guidelines and clinical opinion

Published clinical guidelines suggest that Avastin can be reinitiated once the surgical wound is healed.[16-19]

Additionally, the published guidelines provide a range of recommended delays before reinitiating Avastin treatment, from delays of at least 4 weeks [15-19] to delays of at least 6 to 8 weeks.[20]

Bose et al. proposed an individualised approach, whereby healthy patients with rapid wound healing could resume Avastin after 4 weeks, whilst patients with comorbidities impacting wound healing should extend the postoperative interval by re-initiating Avastin after 6 to 8-weeks.[19]

Roche has no recommendations on stopping or starting Avastin in relation to minor surgery, such as the surgical implant of venous access devices. Timing of minor surgery would be a clinical decision, and local label must be consulted.

Pivotal Avastin clinical trials

Minor surgery in clinical trials were classed as procedures not involving general anaesthesia or respiratory assistance.[21,22]

In clinical trials, minor surgical procedures, including fine needle aspiration, core biopsies, central venous access device placement, arose within 2-7 days of a patient's first dose of Avastin in the trial.[9,22]

Many of the Avastin clinical trial protocols do not provide guidance on when to resume Avastin after minor surgery, though one pivotal clinical trial's protocol mentioned that a treatment delay was not required for minor procedures such as removal or insertion of a central venous catheter.[9]

Published guidelines and clinical opinion on withholding Avastin following surgical implant of venous access devices

There is limited evidence and lack of consensus regarding withholding Avastin treatment following surgical implant of venous access devices.[15,23-25]

Observational retrospective studies have demonstrated a reduced risk of subsequent wound complications associated with Avastin, if Avastin is withheld for a period of 7 to 14 days after device implantation.[15,23-25]

Other analyses provided an alternative view, stating that the complications in central venous port placement were not affected by the timing of Avastin initiation after port implantation.[26,27]

1. Roche Internal Regulatory Document, accessed 7-September 2023 .
2. Food and Drug Administration. Center for Drug Evaluation and Research approval package for: application number: STN-125085/0: medical review(s):69-70. . https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/STN-125085_Avastin_medr_P1.pdf
3. Food and Drug Administration. Center for Drug Evaluation and Research approval package for: application number: BLA 125085 / supp 0074: clinical review(s):15. https://www.accessdata.fda.gov/drugsatfda_docs/bla/2006/125085_0074_avastin.pdf
4. Roche Internal Clinical Trial Procotol (ML18147) 2012.
5. Roche Internal Clinical Trial Protocol (AVAIL) 2005.
6. Roche Internal Clinical Trial Protocol (AVF3694g) 2005.
7. Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 2014;32:1302-8. https://www.ncbi.nlm.nih.gov/pubmed/24637997
8. Socinski M, Jotte R, Cappuzzo F, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med 2018;378:2288-2301. https://www.ncbi.nlm.nih.gov/pubmed/29863955
9. Tewari K, Burger R, Enserro D, et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol 2019;37:2317-2328. https://www.ncbi.nlm.nih.gov/pubmed/31216226
10. Perren T, Swart A, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011;365:2484-96. https://www.ncbi.nlm.nih.gov/pubmed/22204725
11. Aghajanian C, Blank S, Goff B, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 2012;30:2039-45. https://www.ncbi.nlm.nih.gov/pubmed/22529265
12. Roche Internal Clinical Trial Protocol (AVADO) 2013.
13. Wick W, Gorlia T, Bendszus M, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med 2017;377:1954-1963. https://www.ncbi.nlm.nih.gov/pubmed/29141164
14. Roche Internal Clinical Trial Protocol (GOG-0240) 2014.
15. Miles D, Bridgewater J, Ellis P, et al. Using bevacizumab to treat metastatic cancer: UK consensus guidelines. Br J Hosp Med (Lond) 2010;71:670-7. https://www.ncbi.nlm.nih.gov/pubmed/21135762
16. Shord S, Bressler L, Tierney L, et al. Understanding and managing the possible adverse effects associated with bevacizumab. Am J Health Syst Pharm 2009;66:999-1013. https://www.ncbi.nlm.nih.gov/pubmed/19451611
17. Sharma K, Marcus J. Bevacizumab and wound-healing complications: mechanisms of action, clinical evidence, and management recommendations for the plastic surgeon. Ann Plast Surg 2013;71:434-40. https://www.ncbi.nlm.nih.gov/pubmed/22868316
18. Gordon C, Rojavin Y, Patel M, et al. A review on bevacizumab and surgical wound healing: an important warning to all surgeons. Ann Plast Surg 2009;62:707-9. https://www.ncbi.nlm.nih.gov/pubmed/19461291
19. Bose D, Meric-Bernstam F, Hofstetter W, et al. Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care. Lancet Oncol 2010;11:373-82. https://www.ncbi.nlm.nih.gov/pubmed/20171141
20. National Comprehensive Cancer Network. Colon Cancer (Version 2.2023). Accessed on 08-Sep-2023. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
21. Cortés J, Caralt M, Delaloge S, et al. Safety of bevacizumab in metastatic breast cancer patients undergoing surgery. Eur J Cancer 2012;48:475-81. https://www.ncbi.nlm.nih.gov/pubmed/22196033
22. EPAR Avastin EU Risk Management Plan (version 34.0). Available at https://www.ema.europa.eu/en/documents/rmp-summary/avastin-epar-risk-management-plan_en.pdf. Accessed on August 25, 2023.
23. Kriegel I, Cottu P, Fourchotte V, et al. Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy. Anticancer Drugs 2011;22:1020-3. https://www.ncbi.nlm.nih.gov/pubmed/21970853
24. Zawacki W, Walker T, DeVasher E, et al. Wound dehiscence or failure to heal following venous access port placement in patients receiving bevacizumab therapy. J Vasc Interv Radiol 2009;20:624-7; quiz 571. https://www.ncbi.nlm.nih.gov/pubmed/19328717
25. Erinjeri J, Fong A, Kemeny N, et al. Timing of administration of bevacizumab chemotherapy affects wound healing after chest wall port placement. Cancer 2011;117:1296-301. https://www.ncbi.nlm.nih.gov/pubmed/21381016
26. Shigyo H, Suzuki H, Tanaka T, et al. Safety of Early Bevacizumab Administration after Central Venous Port Placement for Patients with Colorectal Cancer. Cancers (Basel) 2023;15:https://www.ncbi.nlm.nih.gov/pubmed/37190192
27. Kretzschmar A. 629 POSTER Starting bevacizumab shortly after venous access device implantation appears not to increase wound healing/bleeding complications nor catheter related thromboses — preliminary results from First BEAT. EJC 2005;3:177.